The adrenal gland produces hormones that affects development and stress, growth, and also helps to regulate kidney function. There are two parts of the adrenal glands, the adrenal cortex and the adrenal medulla. The adrenal cortex produces mineralocorticoids, which regulate salt and water balance within the body, glucocorticoids (including cortisol) which have a wide number of roles within the body, and androgens, hormones with testosterone-like function. The adrenal medulla produces epinephrine and norepinephrine.
Conditions related to adrenal gland activity interfere with the normal functioning of the adrenal glands. Examples of such conditions include, but are not limited to, aldosteronism, primary aldosteronism, secondary aldosteronism, hyperaldosteronism, primary hyperaldosteronism, secondary hyperaldosteronism, adrenal insufficiency, Addison's Disease, adrenoleukodystrophy, pheochromocytoma, Cushing's Syndrome, adrenal hyperplasia, congenital adrenal hyperplasia, cancer, adrenal cancer, hypertension, primary hypertension, secondary hypertension, virilization, congenital syndromes leading to excessive corticosteroid production, Conns or other syndromes of excessive steroid production, and adrenocortical cancer (ACC).
ACC is a malignancy of the adrenal cortex with a poor 5-year survival rate of 10-20%. A majority of cases are metastatic at the time of diagnosis, with the most common sites of spread being the local periadrenal tissue, lymph nodes, lungs, liver, and bone. AC is relatively rare, however, accounting for just 0.02-0.2% of all cancer-related deaths. Detection of tumors at an early clinical stage is crucial for curative resection. Many ACC patients have no symptoms until their tumors reach a large size.
Currently, there is no reasonably sensitive or specific way to distinguish ACC from the much more common benign adenomas. Diagnosis is made on the basis of tumor size and histopathological features that can be summarized by the Weiss score. Weiss scores of 0 or 1 are considered benign, 2 and 3 are ambiguous, and 4 or larger are cancerous. Histological diagnosis of AC is difficult to make, which makes treatment decisions complicated.
Current therapy is often ineffective and may also be associated with intolerable side effects. Indeed, ACC has a poor prognosis in most cases because no existing drugs can halt tumor growth indefinitely and because the high levels of circulating steroids that are produced by many tumors suppress immune responses and disrupt other physiological functions. Current combination treatments that are used to counteract tumor growth and to suppress excess steroid production are plagued by adverse effects, treatment resistance, and drug interactions that can compromise efficacy.
Improved treatments for condition related to adrenocortical activity and/or excessive steroid production are needed.
The present invention addresses this need.